Page 1979 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 115 Transfusion of Plasma and Plasma Derivatives 1753

Emerging Indications reasonably summarized in this chapter. For further information, some
excellent reviews are cited in the reference section. A brief summary
Serum albumin has been shown to be a free radical scavenger. Because of some of the more well-established uses of IVIg are presented in
of this function, some have recommended albumin as an adjuvant the following section.
therapy in patients with sepsis. There are no confirmed data on the
benefits of albumin therapy in this patient population, however. In
other conditions associated with systemic inflammation such as acute Primary Immunodeficiency Syndromes
lung injury or acute respiratory distress syndrome, albumin therapy
use was found to improve oxygenation and hemodynamic status. Primary congenital immunodeficiency syndromes have been treated
with intramuscular Ig for the past 30 years. The use of intramuscular
Ig has certain disadvantages: delayed absorption, delivery of inadequate
Dose amounts because of small muscle mass, and pain at the injection site.
IVIg overcomes these disadvantages, and used prophylactically in
The volume and speed of administration should be determined by patients with primary immunodeficiency has been demonstrated to
the patient’s volume status, condition, and response to the product. reduce the number of febrile and infectious episodes as well as improve
In an adult, the total daily dose should not exceed the theoretical survival rate. IVIg use in IgG subclass deficiencies is also beneficial.
amount present in normal plasma (2g/kg/day), in the absence of
acute hemorrhage. In the pediatric population, albumin dose again
depends on the patient’s condition, but 0.5 to 1.0 g/kg/dose with a Chronic Lymphocytic Leukemia
maximum dose of 6 g/kg/day could be used as a general guideline.
Albumin 5% is oncotically equivalent to normal human plasma. CLL may be associated with hypogammaglobulinemia and complica-
Albumin 25% provides less infusion volume per amount of albumin tions of repeated bacterial infections. IVIg decreases the incidence
and is usually administered to patients with fluid or sodium intake and severity of bacterial infections in CLL patients with hypogam-
restriction. Albumin 25% expands the blood volume by 3.5 times by maglobulinemia and has become accepted prophylactic therapy.
drawing fluid into the intravascular space.
Bone Marrow Transplantation
Adverse Effects
The use of prophylactic IVIg or cytomegalovirus (CMV)–IVIg in
Albumin is a plasma derivative used widely and associated with rare CMV-negative bone marrow transplant recipients during the first
adverse reactions. Allergic reactions, including urticaria, may be 100 days posttransplant has been demonstrated to reduce the
encountered. Changes in vital signs (heart rate, blood pressure, res- incidence of symptomatic CMV-associated disease, including CMV
piration rate), nausea, emesis, and fever/chills have also been rarely interstitial pneumonia, in some trials. Because of the high cost of this
reported. Volume overload and dilutional anemia as well as hypocal- treatment and the increasing use of prophylactic ganciclovir, IVIg is
cemia may occur. Albumin has not been associated with transfusion- currently not indicated for the prophylaxis of CMV infections in
transmitted diseases. bone marrow transplant recipients. In established CMV-interstitial
pneumonia, IVIg in combination with ganciclovir has been shown
to reduce the mortality rate and has become the recommended treat-
INTRAVENOUS IMMUNOGLOBULIN ment modality. Its role in preventing severe graft-versus-host disease
is unclear. Prolonged IVIg therapy during graft-versus-host disease
IVIg is prepared by fractionation of large pools of human plasma. prevention may suppress humoral immunity recovery.
There are numerous preparations available in the United States and
throughout the world. Subcutaneous preparations of Ig are also now
available. Each preparation is slightly different and has theoretic Pediatric Human Immunodeficiency Virus Infection
advantages and disadvantages and specific licensed indications.
Ideally, IVIg should contain each IgG subclass; retain Fc receptor The defects in humoral and cellular immunity observed in children
activity; have a normal half-life; demonstrate virus neutralization, with HIV infection predispose them to life-threatening bacterial
opsonization, and intracellular killing; and have antibacterial capsular infections. Studies previously demonstrated that the administration
polysaccharide antibody. Furthermore, vasoactive impurities should of IVIg to HIV-infected children could reduce the incidence and
be absent, and no transmissible infectious agents should be present. severity of bacterial infections as well as the frequency of hospitaliza-
The uses of IVIg have been extensively reviewed and the number of tion. More recently, studies have now shown that IVIg does not
theoretical and accepted uses for IVIg is rapidly expanding. improve outcome, likely because of improved medications for HIV
and HIV-associated infections.

Indications
Idiopathic Thrombocytopenic Purpura
IVIg is indicated for replacement of Igs or for its immunomodulatory
effects. Currently, there are six FDA approved indications for IVIg IVIg and Rh immune globulin are routinely and effectively used in
treatment: primary immunodeficiency, pediatric HIV infections, the treatment of acute and chronic ITP. IVIg significantly raises the
secondary immunodeficiency in chronic lymphocytic leukemia platelet count within 5 days in adults with chronic ITP and in
(CLL), idiopathic thrombocytopenic purpura (ITP), Kawasaki children with acute ITP. The mechanism of action of IVIg in ITP is
disease, and allogeneic stem cell transplantation in patients older than unknown; one postulation is Fc receptor blockade decreases the
20 years of age. Some of the FDA indications are no longer applicable, removal of antibody-coated platelets. Other proposed mechanisms
such as in patients with CLL and HIV, given better medications. IVIg include suppressed antiplatelet antibody synthesis, increased antiviral
is also considered first-line therapy for multiple other conditions, immunity, and blockage by antiidiotypic antibodies. In general, IVIg
such as Guillain-Barré syndrome, chronic inflammatory demyelinat- induces responses in most patients within 1 to 2 days. Responses are
ing polyradiculoneuropathy (CIDP), neonatal alloimmune thrombo- of variable duration and are rarely sustained, although maintenance
cytopenia (NAIT), posttransfusion purpura (PTP), myasthenia gravis therapy may be of some value. IVIg may be effective in chronic ITP
and stiff-person syndrome (Table 115.4). An exhaustive review of all refractory to corticosteroids or splenectomy; and may show greater
the known established and investigational uses for IVIg cannot be efficacy in conjunction with corticosteroids.